POS0246 SEQUENTIAL RITUXIMAB AND MEPOLIZUMAB IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS
Authors: A. Bettiol, M. L. Urban, F. Bello, D. Fiori, I. Mattioli, G. Lopalco, F. Iannone, A. Egan, L. Moroni, L. Dagna, M. Caminati, S. Negrini, P. Cameli, M. Folci, P. Toniati, R. Padoan, O. Flossmann, R. Solans-Laqué, L. Losappio, J. Schroeder, M. André, L. Moi, P. Parronchi, F. Conti, S. Sciascia, D. Jayne, A. Vaglio, G. Emmi
Journal: Annals of the Rheumatic Diseases (2022)

Background Rituximab (RTX) is an effective remission-induction treatment in ANCA-associated vasculitides (AAVs). Some reports have suggested that it might be effective also in Eosinophilic Granulomatosis with Polyangiitis (EGPA), to induce and maintain remission of vasculitic manifestations [1,2]. However, its effects for preventing respiratory relapses seem to be poor. Mepolizumab (Mepo) (both 100 and 300mg/month) is effective in improving respiratory manifestations and lung function, while partially controlling also systemic activity [3,4]. Isolated case reports further indicate that the sequential therapy with RTX and Mepo might be effective [5-7]. Objectives The study aimed to investigate the efficacy and safety of a therapeutic regimen based on sequential RTX and Mepo for the control of EGPA. Methods A multicenter, retrospective, cohort study was conducted on adult patients diagnosed with EGPA according to the ACR classification criteria [8] or MIRRA trial criteria [3]. Only patients who received induction therapy with RTX (any dosage), and subsequent treatment with Mepo (100-300 mg/4 weeks) within 12 months from last RTX administration were included. Patients receiving other induction therapies between RTX and Mepo were excluded. The effectiveness of sequential RTX and Mepo was assessed in terms of disease activity (by the Birmingham Vasculitis Activity Score, BVAS) and daily corticosteroid dosage. Safety data were also collected. Results Thirty-four EGPA patients treated with sequential RTX and Mepo were included (59% females, median age of 51 years (IQR 40-58); 41% ANCA positive). In most cases (26/34; 76%), RTX was started at the dosage of 1g q2w, and all except two patients had active disease at time of RTX beginning [median BVAS of 9 (IQR 6-14)]. Specifically, most patients started RTX for the control of systemic manifestations (19/34; 56%), or of both systemic and respiratory symptoms (11/34; 32%). All except one patient were receiving oral corticosteroids, at a median dosage of 25 mg/day (10-38). Mepo was started after a median of 14 months (6-23) from RTX initiation and after a median of 5 months (IQR 3-11) from the last RTX administration. Mepo was used at the dosage of 100mg/4 weeks in 32/34 (94%), mostly for the control of respiratory manifestations (25/34, 74%). At the time of starting Mepo, the median BVAS was 4 (2-8), and median prednisolone dose 10 mg/day (7-15). After a median follow-up of 28 months (IQR 23-33) from starting Mepo, the median BVAS decreased to 1.5 (IQR 0-4) and the median corticosteroid dosage to 5 mg/day (2.5-5), with 7/34 (21%) patients being off steroids. At last follow-up, most patients were off-RTX (28/34), typically due to stable disease remission (20/34; 59%). Both RTX and Mepo were well-tolerated; 5 patients had adverse events on RTX (none serious), and 5 on Mepo (including one serious infection). Conclusion Sequential use of RTX and Mepo seems to be effective for remission induction and maintenance in EGPA. References [1]Emmi, Ann Rheum Dis, 2018 [2]Teixeira, RMD Open, 2019 3. Wechsler, NEJM, 2017 [4]Bettiol, Arthritis Rheumatol, 2021 [5]Shiroshita, Respir Med Case Rep, 2018 [6]Higashitani, Mod Rheumatol Case Rep, 2021 [7]Afiari, Cureus 2020 [8]Masi, Arthritis Rheum, 1990 Table 1. Effectiveness of sequential RTX and Mepo in the 34 patients included in the study RTX beginning Mepo beginning Last follow-up Median time elapsed (IQR) - 14 months (6-23) from RTX beginning 28 months (23-33) from Mepo beginning Dosage 1g q2w (26/34); 100mg/4 weeks (32/34) 6 patients off Mepo; 28 patients off RTX 375mg/m 2 for 4 weeks (8/34) 300mg/4 weeks (2/34) Reason for treatment beginning (manifestations) Systemic (19/34); Respiratory (25/34); - Systemic + respiratory (11/34); Systemic (4/34); Only respiratory (3/34); Remission maintenance (5/34) Other (1/34) BVAS (median, IQR) 9 (6-14) 4 (2-8) 1.5 (0-4) Prednisolone dosage (median, IQR), mg/day 25 (10-38) 10 (7-15) 5 (2.5-5) Disclosure of Interests Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federica Bello: None declared, Davide Fiori: None declared, Irene Mattioli: None declared, Giuseppe Lopalco: None declared, Florenzo Iannone: None declared, Allyson Egan: None declared, Luca Moroni: None declared, Lorenzo Dagna Consultant of: Consultation honoraria from GSK outside the current work, Marco Caminati: None declared, Simone Negrini: None declared, Paolo Cameli: None declared, Marco Folci: None declared, Paola Toniati: None declared, Roberto Padoan: None declared, Oliver Flossmann: None declared, Roser Solans-Laqué: None declared, Laura Losappio: None declared, Jan Schroeder Consultant of: Advisory Board fees from AstraZeneca and GSK, Marc André: None declared, Laura Moi: None declared, paola parronchi Consultant of: Consultation honoraria from GSK and Novartis, Fabrizio Conti: None declared, Savino Sciascia: None declared, David Jayne Consultant of: Consultant for Astra-Zeneca, Aurinia, BMS, Boehringer-Ingelheim, Chemocentryx, Chugai, CSL, GSK, Infla-RX, Janssen, Novartis, Roche/Genentech, Takeda and Vifor, Augusto Vaglio Consultant of: Consultation honoraria from GSK outside the current work, Giacomo Emmi Consultant of: Consultation honoraria from GSK outside the current work